Apparatus and method to convey a fluid

ABSTRACT

An apparatus includes a fluid path, a coupling, and a nozzle. The fluid path is to carry a fluid including one or more microparticles. The coupling is located in the fluid path. The nozzle is located in the fluid path to move the fluid through a stagnant region located near the coupling.

FIELD

The present invention relates to conveying a fluid, and moreparticularly, to conveying a fluid that includes microparticles.

BACKGROUND

In some systems, such as therapeutic systems employed in the treatmentof disease, a fluid is conveyed or delivered to a target, such as acancerous tumor, through a conduit that includes a coupling. For a fluidthat includes microparticles, such as radioactive microparticles orradioactive microspheres, the microparticles can become trapped at thecoupling.

Some microparticles are trapped in gaps that result from mechanicallymismatched components in the coupling. Other microparticles are trappedin regions of stagnant fluid flow, such as regions in which the fluidvelocity is less than the saltation velocity. Corners anddiscontinuities in the coupling can create regions of fluid expansion inwhich the fluid velocity is less than the saltation velocity. A forcefield, such as gravity, can also contribute to the trapping ofmicroparticles. In some systems, more than fifty percent of themicroparticles in the flow become trapped. The trapped microparticlesare not delivered to the target. For systems that attempt to solve thisproblem by conveying the fluid at high pressures, the risk of systemleakage increases.

In a therapeutic system, to achieve effective treatment, substantiallyall microparticles introduced into the system should be delivered to thetarget. Failure to deliver substantially all microparticles to thetarget reduces the effectiveness of the treatment. Similarly, in adiagnostic system, to achieve an accurate diagnosis, substantially allmicroparticles introduced into the system should be delivered to thetarget. Further, for microparticles that constitute a medical device,under delivery of the microparticles to the intended target is anincident reportable to regulatory authorities.

SUMMARY

An apparatus includes a fluid path, a coupling, and a nozzle. The fluidpath is to carry a fluid including one or more microparticles. Thecoupling is located in the fluid path. The nozzle is located in thefluid path to move the fluid through a stagnant region located near thecoupling.

An apparatus includes a fluid path and a coupling. The fluid path is tocarry a fluid including one or more microparticles. The coupling islocated along the fluid path. The fluid path is substantially alignedwith a force field.

A method includes introducing a fluid including one or moremicroparticles into a fluid path including a coupling and aligning thefluid path near the coupling with a force field.

An apparatus includes a coupling including a proximal end and a distalend and a low flow rate fluid path including the coupling to deliver atleast about 90% of a source of high density microparticles from theproximal end of the coupling to the distal end of the coupling.

A method includes coupling a source of high density microparticleshaving high specific activity to a mammal and delivering the highdensity microparticles having high specific activity to the mammal at apressure of between about 5 psig and about 30 psig at the source.

A method includes delivering one or more microparticles to a subject,and imaging the one or more microparticles to form image data.

A method includes conveying one or more substantially sphericalmicroparticles to a subject, imaging the one or more substantiallyspherical microparticles to form image data, and analyzing the imagedata to identify an anomalous condition.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1( a) is a perspective view of an apparatus to convey a fluid inaccordance with some embodiments.

FIG. 1( b) is an illustration of a cross-sectional view at line x-x ofthe apparatus shown in FIG. 1( a) and including a fluid path and acoupling located in the fluid path and substantially aligned along thefield lines of a force field in accordance with some embodiments.

FIG. 1( c) is block diagram of an apparatus including the apparatusshown FIG. 1( a) and coupled to a source of radioactive microparticlesand a patient for use in connection with therapies, such as cancertherapies, in accordance with some embodiments.

FIG. 1( d) is a flow diagram of a method including introducing a fluidincluding one or more microparticles into a fluid path including acoupling and substantially aligning the fluid path near the couplingwith a force field.

FIG. 2( a) is an illustration of a cross-sectional view of an apparatusincluding the fluid path shown in FIG. 1( a), the coupling shown in FIG.1( a) and located in the fluid path shown in FIG. 1( a), and a nozzlelocated in the fluid path to move a fluid through a stagnant regionlocated near the coupling in accordance with some embodiments.

FIG. 2( b) is a detailed illustration of an apparatus including thecoupling shown in FIG. 2( a), the nozzle, shown in FIG. 2( a), and aflat-face seal and an elastomeric seal in accordance with someembodiments.

FIG. 3 is an illustration of apparatus including a low flow rate fluidpath including a coupling in accordance with some embodiments.

FIG. 4 is a flow diagram of a method including coupling a source of highdensity microparticles having high specific activity to a mammal, anddelivering the high density microparticles having high specific activityto the mammal at a pressure of between about 5 psig and about 30 psig atthe source in accordance with some embodiments.

FIG. 5 is a Summary Table showing catheter size, pressure ranges,equivalent flow rates, and flush volumes for microparticles suitable foruse as the source of microparticles in accordance with some embodiments.

FIG. 6 is a flow diagram of a diagnostic method in accordance with someembodiments.

FIG. 7 is a flow diagram of a diagnostic method including analysis inaccordance with some embodiments.

DESCRIPTION

FIG. 1( a) is a perspective view of an apparatus 100 to convey a fluidin accordance with some embodiments. The apparatus 100 is suitable foruse in connection with systems and devices that convey or deliver afluid. A fluid is a continuous amorphous substance that is readilyreshaped and has a tendency to assume the shape of its container. Theapparatus 100 is not limited to use in connection with a particularfluid or a particular application or industry. Exemplary fluids suitablefor use in connection with the apparatus 100 include liquids and gases.Further embodiments of the apparatus 100 are shown in FIGS. 1( b), 1(c),2(a), and 2(b) and described below.

FIG. 1( b) is an illustration of a cross-sectional view at line x-x ofthe apparatus 100, shown in FIG. 1( a), including a fluid path 102 and acoupling 104 located in the fluid path 102 and substantially alignedalong the field lines of a force field 106 in accordance with someembodiments. The fluid path 102 includes a proximal end 108 and a distalend 110 and provides a path or conduit to convey or deliver a fluid fromthe proximal end 108 to a distal end 110. The delivery of a fluidintravenously for therapeutic use in the treatment of disease is oneexemplary application of the apparatus 100. In one illustrativeembodiment, the apparatus 100 provides for the delivery of a fluid, suchas a fluid including one or more radioactive microparticles, to a humanvascular system for the treatment of cancer. Liver cancer is anexemplary disease for which therapies have been developed that canbenefit from the use of the apparatus 100. Cancer and other diseasestates can be diagnosed using microparticle injections. Themicrovascular bed of cancer lesions, or other diseases, and surroundinghealthy tissue can be characterized to allow treatment planning,including but not limited to the number of therapeutic microspheres andthe specific activity of the therapeutic microspheres in a subsequenttreatment. Other treatments can be planned from the knowledge of themicrovascular bed.

In some embodiments, the fluid path 102 is formed from a conduit, suchas a tube or microtube. A tube is a conduit that has an inside diametergreater than a few thousand microns. A microtube is a tube that has aninside diameter a between about a fraction of a micron and a fewthousand microns. The inside diameter of the conduit is not limited to aparticular value. For the transport of a fluid that includes one or moremicroparticles or microspheres along the fluid path 102, the fluid path102 is formed from a conduit of sufficient diameter to allow themicroparticles to flow unimpeded from the proximal end 108 to the distalend 110. For example, to transport a fluid that includes five micrometerdiameter microparticles, in some embodiments the inside diameter of aconduit that forms the fluid path 102 is between about twenty-fivemicrometers and about fifty micrometers. The conduit can be flexible orinflexible. Exemplary materials suitable for use in connection with thefabrication of the conduit that forms the fluid path 102 includepolystyrene, plastic, and metals, such as stainless steel.

The coupling 104 included in the fluid path 102 provides a mechanicalconnection or link between two or more objects, such as two or morepieces of conduit 112 and 114 or between a conduit and a catheter. Acoupling can be formed separately from the objects to be connected orthe coupling can be integrated with the objects. The coupling 104 is notlimited to a particular type of coupling. Various couplings, connectors,and fittings are suitable for use in forming the coupling 104 in thefluid path 102 of the apparatus 100.

A Luer connector is one type of coupling used as an interconnectioncomponent in vascular fluid delivery systems. A Luer connector includesa tapered barrel and a conical male part that fits into the barrelwithout a seal. In some embodiments, the taper is about six percent. Foruse in a vascular fluid delivery system, in some embodiments, theapparatus 100 includes a Luer connector for the coupling 104 in thefluid path 102. The coupling material is selected to be compatible withthe fluid and the environment and operating conditions, such astemperature and pressure, of the fluid path 102.

In operation, the apparatus 100 conveys a fluid, such as a fluidincluding one or more microparticles, along the fluid path 102. Amicroparticle may be spherical but it need not be spherical. Solid orhollow glass or glass composite beads can form microparticles suitablefor use in connection with the apparatus 100. In some embodiments, eachof the one or more microparticles has a specific gravity of more thanabout 1.5.

The term microparticle includes nanoparticles, microparticles, andmicrospheres. Nanoparticles include particles and nanospheres having adiameter of about fifty nanometers to about 1000 nanometers.Microparticles include particles having a diameter of between about 1 μmto about 1000 μm. Microspheres include substantially spherical elementshaving a diameter between about 1 μm and about 1000 μm. Exemplarymaterials suitable for use in forming microparticles include inorganic,organic, polymer, radioactive and magnetic materials. Inorganicmaterials include metals, silica, alumina, titania, glass, and ceramic.Organic materials include polystyrene, melanin, and polylactide. Polymermaterials include polyurethane, lignin, polyamide, silicone, copolymersand trimers. A radioactive material exhibits the spontaneous emission ofa stream of particles or electromagnetic rays during nuclear decay. Thestream may include atomic or subatomic particles that may be chargedpositively or negatively. Alpha particles and positrons are exemplarypositively charged particles. Beta particles are exemplary negativelycharged particles. Radioactive materials include radioactive oxides andradioactive polymers. A magnetic material responds to a magnetic field.Magnetic materials include some metals, such as iron, ferromagnetic, andparamagnetic materials. The surface of a microparticle is not limited tobeing formed from a particular material.

Also, in operation, the fluid path 102 near the coupling 104 issubstantially aligned with the force field 106. The fluid path 102 issubstantially aligned with the force field 106 when the angle betweenthe direction of travel of microparticles in the fluid path 102 and thedirection of the force field 106 is between about thirty-five degreesand about forty-five degrees. The fluid path 102 is very substantiallyaligned with the force field 106 when the angle between the direction oftravel of microparticles in the fluid path 102 and the direction of theforce field is less than about thirty-five degrees. When the fluid path102 is very substantially aligned with the force field 106 fewer of theparticles in the fluid path 102 will become trapped than when the fluidpath 102 is substantially aligned with the force filed 106. The forcefield 106 is not limited to a particular type of force field. Exemplaryforce fields suitable for use in connection with the apparatus 100include gravitational force fields, magnetic force fields, centrifugalforce fields, and electric force fields. The force field 106 can bestatic or dynamic. A static force field does not vary with time. Adynamic force field varies with time.

The substantial alignment of the fluid path 102 near the coupling 104with the force field 106 reduces the likelihood of the microparticlesbeing trapped in a gap 116 created in mismatched fittings of thecoupling 104. Further, fewer microparticles enter a stagnant fluidregion 118 at a re-entrant corner 120, when the fluid path 102 issubstantially aligned with the force field 106. Finally, microparticlesthat enter the stagnant fluid region 118 travel in the direction of theforce field 106 into a turbulent region 122 where they are re-entrainedor pulled into the fluid flow of the fluid path 102.

FIG. 1( c) is block diagram of an apparatus 130 including the apparatus100, shown FIG. 1( b), coupled to a source of radioactive microparticles132 and a patient 134 for use in connection with therapies, such ascancer therapies, in accordance with some embodiments. The source ofradioactive microparticles 132 includes a container, such as a vial, tohold a fluid including radioactive microparticles. The container iseither shielded or maintained in a shielded case to provide protectionfrom the radiation emitted by the radioactive microparticles 132. Acatheter 136 can provide a coupling from the fluid path 102 of theapparatus 100 to the patient 134. The catheter 136 is a hollow flexibletube for insertion into a body cavity, duct, or vessel to allow thepassage of fluids. In some embodiments, the apparatus 100 is included inthe catheter 136.

FIG. 1( d) is a flow diagram of a method 140 including introducing afluid including one or more microparticles into a fluid path including acoupling (block 142), and substantially aligning the fluid path near thecoupling with a force field (block 144). In some embodiments, aligningthe fluid path near the coupling with the force field includes aligningthe fluid path near the coupling with a gravitational field. In someembodiments, the method 140 further includes introducing a cancerpatient into the fluid path. And in yet other embodiments, introducingthe fluid including one or more microparticles into the fluid pathincluding the coupling includes introducing a slurry of radioactivemicroparticles under pressure into the fluid path. In some embodiments,the method further includes introducing a flushing fluid having a volumeof between about twenty millilitres and about eighty millilitres intothe fluid path at an operating pressure of about thirty pounds persquare inch per square inch gauge.

FIG. 2( a) is an illustration of a cross-sectional view of an apparatus200 including the fluid path 102, shown in FIG. 1( a), the coupling 104,shown in FIG. 1( a), located in the fluid path 102, and a nozzle 202located in the fluid path 102 to move a fluid through a stagnant region204 located near the coupling 104. The nozzle 202 includes an input port206 and an output port 208. In some embodiments, the nozzle 202 includesa side port 210. The nozzle 202 is not limited to a particular number ofside ports. In some embodiments, the nozzle 202 includes the side port210 and one or more additional side ports, such as side port 211.

The fluid path 102 includes the proximal end 108, shown in FIG. 1( b),and the distal end 110, shown in FIG. 1( b), and provides a path orconduit to convey or deliver a fluid from the proximal end 108 to thedistal end 110. The delivery of a fluid intravenously for therapeuticuse in the treatment of disease is one exemplary application of theapparatus 200. In one illustrative embodiment, the apparatus 200provides for the delivery of a fluid, such as a fluid including one ormore radioactive microparticles, to a human vascular system for thetreatment of cancer. Liver cancer is an exemplary disease for whichtherapies have been developed that can benefit from the use of theapparatus 200.

In operation, all microparticles that enter the fluid path 102 at theproximal end 108 of the apparatus 200 should enter the nozzle 202 at theinput port 206 and should exit the apparatus 200 at the distal end 110.The stagnant region 204 is an interior area of the coupling 104 in whichmicroparticles entering the coupling 104 at the input port 206 of thenozzle 202 can become trapped. When microparticles become trapped in thestagnant region 204 they do not pass through the coupling 104 to thedistal end 110. In some systems, such as therapeutic systems, it isdesirable to keep the number of trapped microparticles low.

Introduction of the nozzle 202 into the fluid path 102 changes thedynamics of the fluid flow in the coupling 104. In some embodiments, theinput port 206 of the nozzle 202 has an input port cross-sectional areaand the output port 208 has an output port cross-sectional area. Makingthe cross-sectional area of the input port 206 greater than thecross-sectional area of the output port 208 reduces the likelihood thatmicroparticles traveling along the fluid path 102 will become trapped inthe stagnant region 204. In some embodiments, the output port 208 has adiameter of between about 0.2 millimeters and about 1 millimeter. Insome embodiments, the output port 208 cross-sectional area is aboutforty percent of the input port 206 cross-sectional area. In someembodiment, the output port 208 diameter is equal to between about fivemicroparticle and about ten microparticle diameters. In addition, makingthe cross-sectional area of the input port greater than thecross-sectional area of the output port forces fluid flow through theside port 210 to assist in moving microparticles through the stagnantregion 204.

The velocity of the fluid at the output port 208 of the nozzle 202creates a low pressure region to draw fluid and microparticles from thestagnant region 204 into the fluid path 102. Further, the nozzle 202occupies a volume in the coupling 104 which increases the flow rate andentrainment of microparticles into the fluid path 102 near the nozzle202. In addition, positioning the output port 208 of the nozzle 202beyond the stagnant region 204 results in delivery of substantially allmicroparticles in the fluid to a location in the coupling 104 beyond thestagnant region 204.

The nozzle 202 includes a nozzle fluid path 212 located between theinput port 206 and the output port 208. In some embodiments, the nozzlefluid path 212 includes a taper 214. In some embodiments, the slope ofthe taper 214 is less than about forty-five degrees. The slope of thetaper 214 is the largest slope of the curve of the nozzle fluid path 212between the input port 206 and the output port 208. For the taper 214having a slope of less than about forty-five degrees, the likelihood ofmicroparticle bridging along the nozzle fluid path 212 is reduced.Microparticle bridging occurs when a group of microparticles block orpartially block the nozzle fluid path 212.

In some embodiments, the nozzle 202 includes the side port 210. The sideport 210 is an opening located on a side surface of the nozzle 202.Introduction of the side port 210 into the nozzle 202 changes thedynamics of the fluid flow in the coupling 104. The side port 210provides a fluid path through the stagnant region 204 for a fluidentering the nozzle 202 at the input port 206. The side port 210 islocated near the input port 206 of the nozzle 202. Further, as describedabove, making the cross-sectional area of the input port 206 greaterthan the cross-sectional area of the output port 208 creates a backpressure to force more fluid flow through the side port 210. The fluidflow at the side port 210 induces turbulence near the nozzle 202 thatsweeps microparticles from the stagnant region 204 near the nozzle 202into the fluid path 102. The fluid flow provided by the side port 210 tothe stagnant region 204 removes substantially all microparticles fromthe stagnant region 204.

The side port 210 is not limited to a particular shape. In someembodiments, the side port 210 is substantially a cylindrical passagethat has a diameter at least as large as the largest microparticle.However, to reduce the likelihood of blockage by bridging, the side portdiameter should be at least two or more microparticle diameters. In someembodiments, the side port diameter is about 0.25 millimeters.

The nozzle 202 is not limited to a particular number of side ports. Theside port 210 can be replicated along the perimeter of the nozzle 202.The replication of the side port 210 is not limited to a particularconfiguration. In some embodiments, the side port 210 includes two ormore side ports spaced a substantially equal distance from each otheralong the perimeter of the nozzle 202. In some embodiments, the sideport 210 includes four side ports with each of the four side portsspaced a substantially equal distance from each other along theperimeter of the nozzle 202.

In some embodiments, the nozzle 202 includes a nozzle flange 216. Thenozzle flange 216 is sized and centered in the coupling 104 to form aseal at the leading edge of the nozzle flange 216. The purpose of theseal between the nozzle flange 216 and the coupling 104 is tosubstantially prevent formation of the gap 116. Preventing formation ofthe gap 116 reduces the number of potential sites that can trapmicroparticles in the coupling 104.

In operation, a fluid enters the apparatus 200 at the proximal end 108and flows along the fluid path 102 through the coupling 104 and thenozzle 202 and exits the coupling 104 at the distal end 110. For a fluidthat includes one or more microparticles, the coupling 104 and thenozzle 202 provide a fluid flow that keeps the number of microparticlestrapped in regions of the coupling 104, such as the stagnant region 204,low.

FIG. 2( b) is a detailed illustration of an apparatus 220 including thecoupling 104, shown in FIG. 2( a), the nozzle 202, shown in FIG. 2( a),and a flat-face seal 222 and an elastomeric seal 224 in accordance withsome embodiments. In some embodiments, the nozzle 202 includes thenozzle flange 216. The flat-face seal 222 is formed between in thecoupling 104 and the nozzle flange 216. A flat-face seal includes asurface-to-surface seal between the two components. In some embodiments,the coupling 104 includes the elastomeric seal 224. The elastomeric seal224 is formed by a ring of elastomeric material compressed between thetwo components of the coupling 104.

The apparatus 200, shown in FIG. 2( a) and the apparatus 220 shown inFIG. 2( b) can be included in a fluid delivery system coupled to apatient. In such embodiments, each of the apparatus 200 and 220 enableseffective infusions of high density, high potency microparticles at lowinfusion pressure and flow rates. The low infusion pressure reduces thelikelihood of leakage. The low flow rate reduces the possibility ofreflux (back flow into a patient's vasculature) which in turn increasesthe likelihood that the microparticles will be delivered to the target.

FIG. 3 is an illustration of apparatus 300 including a low flow ratefluid path 302 including a coupling 304 in accordance with someembodiments. The coupling 304 has a proximal end 306 and a distal end308. In operation, the low flow rate fluid path 302 including thecoupling 304 delivers at least about 90% of a source of high densitymicroparticles from the proximal end 306 to the distal end 308 of thecoupling 304. For example, if a source of high density microparticlesincludes ten million particles, then in operation the apparatus 300delivers at least about nine million high density microparticles fromthe source to the distal end 308 of the coupling 304. A catheter is anexemplary coupling suitable for use in connection with the apparatus300. In some embodiments, in operation, the low flow rate fluid path 302has a flow rate of between about 0.05 millilitres per second and about0.93 millilitres per second. A high density microparticle has a specificgravity of greater than about 1.5. A high specific activity radioactivemicroparticle has a specific activity of greater than about 0.5 Ci/g.For non-radioactive particles, high specific activity refers to theconcentration of active ingredient, for example, a therapeutic drug orenhancing drug such as an oxidizing agent. The apparatus 300 improvesmicroparticle delivery to a target and is particularly useful when thevolume in the coupling 304 available to trap microparticles exceedsabout 5% of the volume of the microparticles intended for delivery tothe target.

FIG. 4 is a flow diagram of a method 400 including coupling a source ofhigh density microparticles having high specific activity to a mammal(block 402), and delivering the high density microparticles having highspecific activity to the mammal at a pressure of between about 5 psigand about 30 psig at the source (block 404). In some embodiments,coupling the source of high density microparticles having high specificactivity to the mammal includes connecting a catheter between the sourceand the mammal. In some embodiments, delivering the high densitymicroparticles having high specific activity to the mammal at thepressure of between about 5 psig and about 30 psig at the sourceincludes delivering more than about 90% of the high densitymicroparticles available at the source to the mammal.

FIG. 5 is a Summary Table showing catheter size, pressure ranges,equivalent flow rates, and flush volumes for microparticles suitable foruse as the source of microparticles in accordance with some embodiments.As can be seen in the Summary Table, for a catheter size of 3 French,the pressure range in the fluid path 302, shown in FIG. 4, is betweenabout 5 psig and about 30 psgi. The equivalent flow is 0.49±0.44 mL/sand the flush volume is less than about 60 ml. For a catheter size of 5French, the pressure range in the fluid path 302, shown in FIG. 4, isbetween about 5 psig and about 30 psig. The equivalent flow is 2.1±0.9and the flush volume is less than about 60 ml. The flow rate variabilityis based on three standard deviations. Flow rate values for 4 Frenchcatheters fall between the 3 and 5 French values. At the pressures andflow rates for the fluid path shown in the Summary Table, a source ofhigh density microparticles can include a seal rated for a lowerpressure than for higher pressure fluid paths.

FIG. 6 is a flow diagram of a diagnostic method 600 in accordance withsome embodiments. The method 600 includes delivering one or moremicroparticles to a subject (block 602), and imaging the one or moremicroparticles to form image data (block 604). The image data can beanalyzed by a physician, clinician, or a computing system to generate adiagnosis. The image data is not limited to a particular type of data.Exemplary types of data include digital, such as digital data stored ina computing system, analog, such as photographs or other displayableimages, and mixed digital and analog. In some embodiments, deliveringthe one or more microparticles to the subject includes delivering theone or more microparticles to a microvascular bed. A microvascular bedincludes the small vascular structures in organs, such as the humanliver. These small vascular structures can trap substantially sphericalmicroparticles. In some embodiments, delivering the one or moremicroparticles to the subject includes delivering one or moreradioactive microparticles to the subject. In some embodiments,delivering the one or more microparticles to the microvascular bedincludes delivering the one or more microparticles to the microvascularbed in a human liver or other human organ. In some embodiments,delivering the one or more microparticles to the microvascular bedincludes delivering one or more radioactive microparticles to themicrovascular bed in a human liver, breast, brain, or other human organ.The imaging of the microparticles is not limited to a particular method.Any method of imaging capable of detecting microparticles or clusters ofmicroparticles is suitable for use in connection with the method 600.Exemplary imaging methods include ultrasound, magnetic resonanceimaging, and computer aided tomography.

FIG. 7 is a flow diagram of a diagnostic method 700 including analysisin accordance with some embodiments. The method 700 includes conveyingone or more substantially spherical microparticles to a subject (block702), imaging the one or more substantially spherical microparticles toform image data (block 704), and analyzing the image data to identify ananomalous condition (block 706). Cancer is one example of an anomalouscondition that can be detected and analyzed using the method 700. Themethod 700 also includes delivering a small numbers of radiocativemicroparticles a subject, such as an animal, analyzing the location anddistribution of the microparticles in the subject, and a generating atreatment regime from the analysis. The treatment regime can includedelivering a larger number of substantially spherical microparticles tothe subject. In some embodiments, conveying the one or moresubstantially spherical microparticles to a subject includes conveyingone or more radioactive microparticles to the subject. In someembodiments, analyzing the image data to identify the anomalouscondition includes comparing the image data against data that identifiesknown diseases to identify a an animal disease state. In someembodiments, imaging the one or more substantially sphericalmicroparticles to form image data includes imaging using a magneticresonance imaging system. However, the methods of imaging are notlimited to a particular method. Any imaging method capable of detectingmicroparticles can be used in connection with the described diagnosticmethods. Exemplary imaging systems include systems that image usingwaves, such as electromagnetic or acoustic waves. Exemplary imagingsystems that use electromagnetic waves include magnetic resonanceimaging and computer aided tomography. Exemplary imaging systems thatuse acoustic waves include ultrasound imaging systems.

Although many alterations and modifications of the described embodimentswill no doubt become apparent to a person of ordinary skill in the artafter having read the foregoing description, it is to be understood thatany particular embodiment shown and described by way of illustration isin no way intended to be considered limiting. Therefore, references todetails of various embodiments are not intended to limit the scope ofthe claims.

1.-32. (canceled)
 33. A method comprising: delivering one or moremicroparticles to a subject; and imaging the one or more microparticlesto form image data.
 34. The method of claim 33, wherein delivering theone or more microparticles to the subject comprises: delivering the oneor more microparticles to a microvascular bed.
 35. The method of claim33, wherein delivering the one or more microparticles to the subjectcomprises: delivering one or more radioactive microparticles to thesubject.
 36. The method of claim 34, wherein delivering the one or moremicroparticles to the microvascular bed comprises: delivering the one ormore microparticles to the microvascular bed in a human liver.
 37. Themethod of claim 34, wherein delivering the one or more microparticles tothe microvascular bed comprises: delivering one or more radioactivemicroparticles to the microvascular bed in a human liver.
 38. A methodcomprising: conveying one or more substantially spherical microparticlesto a subject; imaging the one or more substantially sphericalmicroparticles to form image data; and analyzing the image data toidentify an anomalous condition.
 39. The method of claim 38, whereinconveying the one or more substantially spherical microparticles to asubject comprises: conveying one or more radioactive microparticles tothe subject.
 40. The method of claim 38, wherein analyzing the imagedata to identify the anomalous condition comprises: comparing the imagedata against data that identifies known diseases to identify a an animaldisease state.
 41. The method of claim 38, wherein imaging the one ormore substantially spherical microparticles to form image datacomprises: imaging using a magnetic resonance imaging system.